Is KRT12 p.Pro15Ser (c.43C>T) pathogenic?

KRT12 p.Pro15Ser (c.43C>T) is classified Benign in KRT12 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0653); Common (popmax 59%, eas) — too common for a highly-penetrant pathogenic allele; Associated with corneal dystrophy, Meesmann, 1.

What condition is associated with KRT12 p.Pro15Ser (c.43C>T)?

KRT12 p.Pro15Ser (c.43C>T) is associated with corneal dystrophy, Meesmann, 1 (ClinVar).

How is Meesmann corneal dystrophy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about KRT12 p.Pro15Ser (c.43C>T)?

AlphaMissense predicts likely benign (score 0.0653) — an in-silico prediction, not a clinical call.

KRT12 p.Pro15Ser

Q: How common is KRT12 p.Pro15Ser (c.43C>T) in the general population?

KRT12 p.Pro15Ser (c.43C>T) is common (popmax 59%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.43C>T · rs11650915 · VCV66128

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0653 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 59%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

corneal dystrophy, Meesmann, 1

Computational evidence

Protein change
AlphaMissense	0.0653	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -4.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.17	GERP -3.6
Regional constraint	o/e 0.94	unconstrained · MANE · 5,522 bp · p 0.13 · regional, not allelic
Overall
CADD	0.169	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 59% East Asian · 26,478/44,860 alleles

Filtering AF 58.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 58.2%

Overall 34.1% 548,666/1,610,854 alleles · common exomes 503,799/1,458,776 · genomes 44,867/152,078 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	59%	2
Admixed American	48.7%	2
Amishnot grpmax-eligible	46.2%	2
Ashkenazi Jewishnot grpmax-eligible	38.5%	3
European (non-Finnish)	34.1%	3
Middle Eastern	33.7%	3
Finnishnot grpmax-eligible	33.5%	3
Remaining individualsnot grpmax-eligible	33.4%	3
South Asian	30.1%	3
African / African-American	10.5%	9

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: KRT12
Protein: p.Pro15Ser
Coding: c.43C>T
MANE Select: NM_000223
dbSNP: rs11650915
Type: single nucleotide variant
Location: chr17:40867144 (GRCh38)
Gene constraint: LOEUF 0.979 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.57
Residue 15: a UniProt-annotated variant site (in); the 'head' region; the 'disordered' region

Full KRT12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

corneal dystrophy, Meesmann, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Meesmann corneal dystrophy (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

KRT12 p.Met129Thr Pathogenic ★ same condition
KRT12 p.Arg187Gly Uncertain significance ★ ⚠ same condition
KRT12 p.Asp175Asn Conflicting classifications of pathogenicity ★ ⚠ same condition
KRT12 p.Glu330Ter Uncertain significance ★ same condition
KRT12 p.Leu384Pro Uncertain significance ★ ⚠ same condition
KRT12 p.Leu394Pro Conflicting classifications of pathogenicity ★ ⚠ same condition
KRT12 p.Arg135Gly Pathogenic same condition
KRT12 p.Arg135Ile Pathogenic same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/krt12-p-pro15ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown